Pharmacological characterization and preclinical evaluation of 11h: a novel, brain-penetrant PDE4 inhibitor for neurological disorders.

ABSTRACT:

Background

Phosphodiesterase 4 (PDE4) inhibitors hold promise for treating neuroinflammatory and neurodegenerative disorders, but their clinical application in central nervous system (CNS) diseases has been limited by insufficient brain penetration and adverse effects, especially nausea and vomiting. In this study, we characterize compound 11h, a novel, orally available, brain-penetrant PDE4 inhibitor designed to address these limitations.

Methods

11h was evaluated using integrated computational, in vitro, and in vivo approaches, including Schrödinger-based molecular docking against human PDE4A10, luminescence-based cAMP assays for PDE4 isoform inhibition, and inflammatory assays in murine macrophages, microglia-like cells, and human PBMCs. In vivo efficacy, pharmacokinetics

SUBMITTER: Lackovic J 

PROVIDER: S-EPMC12823826 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature